1. Field of the Invention
The present invention relates to live biofilm targeting and subsequent bacterial thermolysis for its eradication in the human body, utilizing secondary quantum optical and thermal emissions from the distal end of near infrared laser delivery fibers.
2. Relevant Technologies
To date, in excess of 300 different species of bacteria have been described in the human oral cavity (Moore W. E., The Bacteria of Periodontal Diseases, Periodontol. 2000). Most bacteria are found in dental plaque and in the sub-gingival periodontal and periimplant pockets. These sub-gingival bacteria have evolved to fight and inhibit the normal host defense system creating a unique ecological niche in the periodontal pocket.
Subgingival bacteria find their nutrient base in the crevicular fluid of the periodontal pocket. Even though these bacteria are in direct proximity to the highly vascularized periodontal and periimplant epithelium, they continue to grow and thrive. Despite (and arguably because of) the host's immune and inflammatory responses seeking to inhibit bacterial colonization and intrusion into the tissues (e.g., mediated by lysozymes, complement formation, bradykinin, thrombin, fibrinogen, antibodies and lymphocytes), subgingival bacteria tend to prevail in the periodontal and/or periimplant pocket providing a unique environmental niche (Cimasoni, Monogr. Oral Sci. 12:III-VII, 1-152 (1983)).
To successfully treat the periodontal and/or periimplant pocket and periodontal/periimplant disease as a whole, the local inflammation and its cause must be eliminated, in an effort to re-establish an intact barrier against the root of the tooth. A newly regenerated periodontal ligament or epithelial barrier connected to the root of the tooth or implant will limit the space available for bacterial growth. Once the cause of the immune and inflammatory responses is eliminated, the periodontal tissues will likely heal. When dealing with implants, the disease is even more recalcitrant and difficult to eliminate, because of the unique and foreign three dimensional architecture and roughened surface of most commercial dental implants.
Healing can be seen as new collagenous and epithelial attachments begin to form in the area just inferior to the base of the periodontal pocket. These new periodontal ligament fibers generally occur only in areas not previously exposed to live bacteria in the pocket. In contrast, the epithelial seal known as long junctional epithelium (i.e., a strong epithelial adaptation to the root surface) generally will occur in areas that were exposed to the live biofilm of the periodontal pocket. With implants (where a periodontal ligament does not exist) new bone formation and/or long junctional epithelium are sought to reduce the available space for bacterial growth.
Traditional Approaches
Periodontal/periimplant instruments have been invented and designed over the years for the specific goal of plaque and calculus removal, root planing and debridement, and removal of diseased periodontal/periimplant tissues. In particular, periodontal scaling, root planing and curettage instruments are the mechanical approaches of choice to remove dental plaque, calculus, diseased cementum, and diseased pocket soft tissues.
A number of pharmacological approaches have been developed as an adjunct to traditional mechanical approaches to attack bacteria (e.g., extended release antimicrobial formulations for delivery in the periodontal/periimplant pocket after mechanical debridement). However, these pharmacological modalities have significant limitations because to be effective they must (a) reach the intended site of action (a deep three-dimensional pocket), (b) remain at an adequate concentration, and (c) last for a sufficient duration of time.
To remain at an adequate concentration and last for a sufficient duration of time, the intrasulcular delivery vectors of the antimicrobials (e.g., resorbable gels, resorbable microspheres, and antimicrobial impregnated chips) must fill the physical space of the periodontal pocket. Most of these vectors stay in place in the periodontal pocket for the duration of the drug delivery therapy (up to three weeks), and hence prevent the immediate healing process of new periodontal attachment and long junctional epithelium formation at the tooth/implant pocket interface after mechanical debridement. In addition, the majority of local antimicrobials used are bacteriostatic, and never fully eliminate periodontal and/or periimplant pathogens from the treatment site. Long term resistant strains often arise in the periodontal pocket in response to sub-lethal antimicrobial absorption. Not surprisingly, these local pharmacological modalities have been reported to have only marginal success rates (The Role of Controlled Drug Delivery for Periodontitis, Position Paper from AAP, 2000) and to have severe limitations ultimately leading to re-infection and continued disease progression.
Recent Developments: The Biofilm Paradigm
The recognition that subgingival dental plaque exists as a living biofilm has shed some light on the underlying mechanism at work (Periodontology 2000 (supra); and Chen, J. Calif. Dent. Assoc. (2001).
Costerton et al., J. of Bacteriol. (1994), have described biofilms as matrix enclosed bacterial populations adherent to each other and/or to surfaces or interfaces. The same researchers have also described biofilms as ecological communities that have evolved to permit survival of bacterial the community as a whole, with specialized nutrient channels within in the biofilm matrix (a primitive circulatory system) to facilitate the movement of metabolic wastes within the colony. If dental plaque and subgingival bacterial colonies are now viewed as a living biofilm, there is a need (not only limited to dentistry) for effective biofilm targeting techniques.
Current understanding of biofilms has conferred upon them some basic properties (Marsh et al., Adv. Dent. Res. (1997)). These include but are not limited to actual community cooperation between different types of microorganisms, distinct and separate microcolonies within the biofilm matrix, a protective matrix surrounding the bacterial colonies, different distinct microenvironments within different microcolonies, primitive communication systems, and unique protection from and resistance to antibiotics, antimicrobials, and the immunological and inflammatory host response.
Most previous attempts to control periodontal diseases have been performed based on traditional understanding of periodontal and periimplant bacteria in in vitro. As a living biofilm (in vivo) however, subgingival plaque and periodontal bacteria act and function quite differently than the classical laboratory models would predict. Periodontal and periimplant bacteria in a live biofilm produce different and more harmful chemicals and enzymes than they do in culture in the laboratory. Also, within a biofilm, there is an increase in the spread of antibiotic resistance through inter-species relationships.
The biofilm (a proteinaceous slimy matrix) itself serves as an effective barrier of protection from many classical therapeutic regimens targeting bacteria. Antibiotics may fail to even penetrate the biofilm and reach the causative bacteria if they are neutralized by resistant enzymatic reactions within the biofilm.
This new understanding of the ethiology underlying periodontal disease has thus identified a void and a need for novel procedures targeting the biofilm directly to combat periodontal disease and the recalcitrant biofilms that harbor and protect the pathogenic bacteria. Such techniques are hereinafter referred to as Biofilm Targeting Technologies (BTT).
Various dyes and other compounds have been proposed for the express purpose of disinfecting or sterilizing tissues in the oral cavity. It has been proposed to selectively target bacteria for laser irradiation with chromophores in the oral environment to expedite bacterial thermolysis. Specifically, there are proposals for treating inflammatory periodontal and periimplant diseases along with other lesions in the oral cavity, by: (a) contacting the tissues, wound or lesion, with a redox agent (dye) such that the bacteria themselves take up the compound, and are inhibited over time, by the exogenous agent in the absence of a laser; or by (b) contacting the tissues, wound or lesion, with a photosensitizing compound (dye) such that the bacteria and/or tissues themselves take up the compound, and then irradiating the tissues or lesion with laser light (generally soft visible red lasers) at the specific wavelength absorbed by the photosensitizing and targeting chromophore.
Despite the large literature relating to the use of dyes and laser irradiation in the context of treatment of oral cavity tissues, there remains a need for effective direct targeting and thermolysis in vivo of the biofilm which would minimize harm to healthy tissues and promote healing.
In view of the foregoing, it would be an advancement in the art to provide new approaches for use in treating periodontal and periimplant disease that addressed the drawbacks of the approaches presently available. In particular, it would be an advancement to provide approaches for the treatment of bacterial fueled inflammatory diseases by effectively targeting and destroying the whole live biofilm (and consequently the bacteria) in the three dimensional periodontal/periimplant space, without harming the healthy dental or other tissues. In particular it would be an advancement to provide novel methods for treating a diseased tissue exploiting optical and thermal emissions of near-infrared diode laser systems and fibers in order to target chromophore stained biofilm while minimizing damage to healthy tissues. Furthermore, it would be a desirable advancement to identify methods and means for targeting disease tissue with increased specificity as evidenced by a better control of the coagulation zone of incision with reduced deeper effects.